Related Experiment Video
Updated: Jul 17, 2026
08:15
Gastrointestinal Motility Monitor (GIMM)
Published on: December 1, 2010
Changes in opioid receptor selectivity following processing of peptide E: effect on gut motility
T P Davis1, T J Gillespie, J Shook
1Department of Pharmacology, University of Arizona College of Medicine, Tucson.
Gastroenterology
|June 1, 1991
Summary
Enzymatic processing of Peptide E shifts its receptor selectivity from mu-opioid to delta-opioid, altering its biological effects. This processing results in a fragment with potent analgesia but no impact on intestinal transit.
Area of Science:
- Pharmacology
- Neuroscience
- Biochemistry
Background:
- Peptide E is a mu-selective opioid peptide derived from proenkephalin A.
- It contains both [Met5]-enkephalin and [Leu5]-enkephalin.
- Central and peripheral processing of Peptide E yields a [Leu5]-enkephalin-containing fragment.
Purpose of the Study:
- To investigate if proteolytic processing alters Peptide E's receptor selectivity.
- To determine the pharmacological profile of the processed fragment, Peptide E-(15-25).
Main Methods:
- In vitro inhibition of electrically stimulated muscle contractions (mouse vas deferens, guinea pig ileum).
- In vivo intracerebroventricular administration in mice to assess analgesia and intestinal transit.
- In vitro radioligand binding assays using rat whole brain homogenates.
Main Results:
- Peptide E-(15-25) demonstrated a sixfold delta-opioid receptor selectivity in vitro.
- Intracerebroventricular administration of Peptide E-(15-25) produced potent naloxone-reversible analgesia without affecting intestinal transit.
- Radioligand binding assays showed Peptide E has mu-opioid affinity, while Peptide E-(15-25) exhibits reduced mu-opioid and maintained delta-opioid affinity.
Conclusions:
- Enzymatic processing of Peptide E to Peptide E-(15-25) results in a shift from mu- to delta-opioid receptor selectivity.
- This shift in selectivity is associated with a different spectrum of biological effects, including analgesia without gastrointestinal effects.
More Related Videos
07:48Tracking Drug-induced Changes in Receptor Post-internalization Trafficking by Colocalizational Analysis
Published on: July 3, 2015
16:02Demonstration of the Sequence Alignment to Predict Across Species Susceptibility Tool for Rapid Assessment of Protein Conservation
Published on: February 10, 2023
Related Concept Videos
01:22Opioid Receptors: Overview
Opioid receptors, including the mu (μ, MOR), delta (δ, DOR), and kappa (κ, KOR) types, belong to the rhodopsin family of G protein-coupled receptors. These receptors are located throughout the central and peripheral nervous systems and in non-neuronal tissues such as macrophages and astrocytes. Opioid receptor ligands can be categorized into agonists or antagonists. Highly selective agonists include [d-Ala2, MePhe4, Gly(ol)5]-enkephalin or DAMGO for MOR, [D-Pen2, D-Pen5]-enkephalin or DPDPE for...
01:25Analgesia and Pain Management
Pain is critical to various clinical pathologies, provoking an urgent need for effective management. Pain, whether acute or chronic, is a complex neurochemical process. Its alleviation depends on the type, with nonopioid analgesics effective for mild to moderate pain, such as musculoskeletal or inflammatory pain, while neuropathic pain responds best to anticonvulsants, tricyclic antidepressants, or serotonin/norepinephrine reuptake inhibitors. For severe acute or chronic pain, opioids may be...
01:15Opioid Analgesics: Synthetic and Semisynthetic Opioids
Synthetic and semisynthetic opioids are pivotal in pain management and tackling opioid addiction. Semisynthetic opioids, including morphinans (morphine derivatives), oxycodone, oxymorphone, hydrocodone, and hydromorphone, have improved pharmacokinetic profiles compared to morphine. Additionally, heroin and 6-MAM (6-Monoacetylmorphine) show better CNS penetration than morphine due to heightened lipid solubility. Hydromorphone, a potent opioid, undergoes hepatic metabolism to form the active...
01:28Drugs Affecting GI Tract Motility: Dopamine Receptor Antagonists
Prokinetic agents are specialized medications that stimulate gastrointestinal (GI) motility, promoting food movement through the GI tract. Dopamine, an inhibitory neurotransmitter, plays a significant role in this process, reducing GI motility and indirectly controlling the speed of digestion. Dopamine receptor antagonists, such as metoclopramide and domperidone, offer a unique advantage as prokinetic agents. By blocking the dopamine receptors, these drugs increase GI motility, improving food...
01:23Drugs Affecting GI Tract Motility: Serotonin Receptor Agonists
Serotonin, a crucial neurotransmitter synthesized by enterochromaffin cells, plays a cardinal role in regulating gastrointestinal (GI) motility. With over 90% of the body's total serotonin in the GI tract, its influence on digestive processes is profound. Serotonin is swiftly released upon various stimuli, such as food boluses or certain drugs, triggering intrinsic sensory neurons in the myenteric plexus and extrinsic vagal and spinal sensory neurons. This leads to the activation of the...
01:17Drugs Affecting GI Tract Motility: Opioids as Antidiarrheal Agents
Diarrhea, a condition marked by frequent loose or watery bowel movements, can be triggered by multiple factors such as viral or bacterial infections, food intolerances, anxiety, medications, and digestive disorders. Symptoms may include abdominal pain, bloating, nausea, and cramping. Severe or prolonged diarrhea can lead to complications like electrolyte imbalances, malnutrition, and dehydration if left untreated.
Opioids, widely used antidiarrheal agents, mitigate diarrhea by slowing down...
Opioids, widely used antidiarrheal agents, mitigate diarrhea by slowing down...